The fate of immunocompromised patients in the treatment of chronic periprosthetic joint infection: a single-centre experience.

PURPOSE: Immunocompromised patients with periprosthetic joint infection (PJI) are rare and currently there are no reliable guidelines according to which these infections can be successfully managed. The purpose of this study was to report the clinical course of different strategies for treatment of PJI in frail patients. METHODS: A retrospective analysis between 2004 and 2015 included 29 immunocompromised patients (13 hips and 16 knees) with chronic PJI who underwent one-stage revision or debridement, antibiotics and implant retention (DAIR). Patients were stratified according to the Musculoskeletal Infection Society (MSIS) staging system and the clinical course included recurrence of infection and functional outcomes which were extracted from patients' charts. The average follow-up was 68 months (range, 26-149 months). RESULTS: Sixteen of the 29 patients had recurrent infections. At last follow-up, 13 patients were on chronic suppressive antibiotic therapy, three patients died but not one death was considered to be related to the infection. A recurrent infection was observed in 13 of the 24 medically compromised hosts (MSIS type B). Sixteen of the 24 patients underwent one-stage revision; another eight of them underwent DAIR. The infection recurred in three of the five patients (60%) with the worst host grades (MSIS type C). One-stage revision was performed in one of the five patients and the remaining four patients received DAIR. CONCLUSION: Our results show that we should compromise our expectation and intemperate treatment for such a population. The goals of PJI treatment in these patients should take into account their preferences and may pay more attention to the concept of disease control rather than cure, especially for patients with severe comorbidities (MSIS C). LEVEL OF EVIDENCE: Therapeutic Level IV.

NFATC1 and NFATC2 expression patterns in human osteochondromas.

Background: Our previous study in genetic mouse models found that NFATc1 and NFATc2 suppress osteochondroma formation from entheseal progenitors. However, it remains unclear whether NFAT signaling is also involved in human osteochondromagenesis. As the first step in addressing this question, the current study aimed to determine the expression patterns of NFATC1 and NFATC2 in human osteochondroma samples. Methods: Immunohistochemistry (IHC) was used to examine and analyze NFATC1 and NFATC2 expression in human osteochondroma samples. The human periosteum was used to map the expression of NFATC1 under physiological conditions by IHC. Furthermore, human periosteal progenitors were isolated and identified from the periosteal tissues of bone fracture healing patients. The expression of NFATC1 in human periosteal progenitors was characterized by Western blotting compared to human bone marrow stromal cells (BMSC). Results: The IHC results showed that the expression of NFATC1 was undetectable in most human osteochondromas cells, and only a small proportion of osteochondroma cells, especially clonally grown chondrocytes, showed positive staining of NFATC1. NFATC2 expression was also undetectable in most chondrocytes in human osteochondromas. The mouse and human periosteum showed a comparable ratio of NFATC1 positive cells (9.56 ± 0.80% vs 11.04 ± 2.05%, P = 0.3101). Furthermore, Western blotting analysis revealed that NFATC1 expression was highly enriched in human periosteal progenitors compared to BMSC. Conclusions: NFATC1 and NFATC2 are undetectable in most human osteochondroma chondrocytes. The expression pattern of NFATC1 in human osteochondromas and the normal periosteum suggests that NFAT signaling could be suppressed during human osteochondromagenesis.

N6-methyladenosine (m6A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m6A/SIRT1 manner.

Increasing evidence suggest the biological roles of N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) in the bone disease, especially osteoarthritis (OA). However, the interaction of m6A and lncRNA in osteoarthritis is still unclear. Here, we found that a m6A-related lncRNA LINC00680 upregulated in the OA tissue and IL-1ß-induced isolated primary chondrocytes. Functionally, in IL-1ß-induced chondrocytes, silencing of LINC00680 recovered the proliferation and repressed the extracellular matrix (ECM) degradation. Mechanistically, m6A methyltransferase METTL3 combined tithe the m6A site of LINC00680 to up-regulate its expression. Moreover, LINC00680 interacted with SIRT1 mRNA through binding at m6A site on SIRT1 mRNA 3'-UTR, thereby enhancing the stability of SIRT1 mRNA. Overall, these findings exhibited a role of LINC00680/m6A/SIRT1 mRNA complex in chondrocytes. Taken together, the present study intends to uncover the mechanism by which METTL3-mediated LINC00680 accelerates OA progression, which may provide novel insight for OA.

Total knee arthroplasty with the least-constrained implant possible for type II valgus knee > 20°: a 3-14 years' follow-up.

OBJECTIVE: To estimate the midterm outcome of primary total knee arthroplasty for severe valgus deformity using selective release of tight lateral structures and the least-constrained implant. METHODS: We performed total knee arthroplasty on 65 consecutive type II knees with valgus deformity> 20°. Surgery was done via a medial parapatellar approach. Conventional bone cutting was done with selective lateral soft tissue release, and the least-constrained total knee prosthesis possible was used. Posterior stabilized implants were employed in most knees, except for three knees that required the implantation of constrained condylar knee prostheses. The average duration of follow-up lasted for 10.5 years. RESULTS: Preoperatively, average valgus was 30.6°, and average range of motion was 43.7° (range, 0-80°). Postoperatively, average valgus was 7.3° and average range of motion was 110.6° (range, 80-130°). The lateral collateral ligament and iliotibial band were released in all knees, and release of the popliteus tendon was required in two knees. Stable flexion and extension gaps were achieved in most cases, except for two that had medial side instability. Follow-up showed that stability was maintained. CONCLUSIONS: This surgical technique combined selective lateral soft tissue release with use of the least-constrained implant possible and was effective for severe valgus deformities of the knee, with good clinical results.

Artesunate alleviates interleukin­1ß­induced inflammatory response and apoptosis by inhibiting the NF­κB signaling pathway in chondrocyte­like ATDC5 cells, and delays the progression of osteoarthritis in a mouse model.

Osteoarthritis (OA) is a progressive and degenerative joint disorder that is highly prevalent worldwide and for which there is currently no effective medical therapy. Artesunate (ART), a natural compound used to treat malaria, possesses diverse biological properties, including the regulation of inflammation and apoptosis in various cells; however, its role in OA remains unclear. The aim of the present study was to investigate the effects of ART on interleukin (IL)­1ß­induced chondrocyte­like ATDC5 cells and in an OA mouse model. The results revealed that ART dose­dependently relieved the inhibitory effect of IL­1ß on cell viability. Moreover, ART significantly reduced the overexpression of matrix metalloproteinase (MMP)­3, MMP­13, a disintegrin and metalloproteinase with thrombospondin motifs­5 and cyclooxygenase­2 at both the gene and protein levels in chondrocyte­like ATDC5 cells stimulated by IL­1ß. Furthermore, ART decreased the expression of pro­apoptotic Bax, cleaved caspase­3 and cleaved caspase­7 in a dose­dependent manner, and increased the expression of the anti­apoptotic factor Bcl­2. These changes were mediated by the inhibitory effect of ART on the nuclear factor­κB signaling pathway, defined as repression of the phosphorylation of IκBα and p65, and improved redistribution of p65. Additionally, ART blocked the advancement of the calcified cartilage zone and the loss of proteoglycan, and lowered histological scoring of OA in a mouse model. Taken together, these results indicate that ART may be of value as a therapeutic agent for OA.

Artesunate, an Anti-Malaria Agent, Attenuates Experimental Osteoarthritis by Inhibiting Bone Resorption and CD31hiEmcnhi Vessel Formation in Subchondral Bone.

Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-ß/Smad2/3 signaling. Additionally, ART abrogated CD31hiEmcnhi vessel formation via downregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31hiEmcnhi vessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA.

Diagnostic value of combined serum marker changes and quantitative MRI evaluation of cartilage volume of tibial plateau in a surgically-induced osteoarthritis dog model.

Objective To evaluate the combined diagnostic value of two serum osteoarthritis (OA) markers and quantitative magnetic resonance imaging (MRI) evaluation of the cartilage volume of the tibial plateau in a canine model of experimental OA. Methods A total of 18 male Beagle dogs were used in this longitudinal study. OA was surgically induced via anterior cruciate ligament transection (ACLT) of the right knee in 10 dogs. The remaining eight dogs formed the sham operation control group and underwent the same procedure without ACLT. At various times after surgery, enzyme-linked immunosorbent assay was used to measure serum C-telopeptide of type II collagen (CTX-II) and type X collagen (ColX) levels. Quantitative evaluation of the tibial plateau volume was undertaken using MRI and ImageJ software. Results The serum CTX-II levels were significantly higher in the OA group at weeks 8, 12 and 16 after surgery, but not at week 4, compared with the control group. The serum ColX levels in the OA group were significantly higher than in the control group at weeks 8 and 12. The tibial plateau cartilage volumes in the OA group were significantly lower than in the control group at weeks 8 and 16. Conclusion Serum CTX-II and ColX levels combined with quantitative MRI evaluation of the tibial plateau cartilage volume in a canine model of OA demonstrated the potential to detect and monitor OA progression.